Triethylamine → N-(2-(5-chloro-1H-indol-3-yl)ethyl)-5-(chloromethyl)isoxazole-3-carboxamide

HRID 1918512

Reaction equation

S(Cl)(Cl)=O.O[CH2:6][C:7]1[O:11][N:10]=[C:9]([C:12]([OH:14])=O)[CH:8]=1.[ClH:15].[Cl:16][C:17]1[CH:18]=[C:19]2[C:23](=[CH:24][CH:25]=1)[NH:22][CH:21]=[C:20]2[CH2:26][CH2:27][NH2:28].C(N(CC)CC)C>ClCCl>[Cl:16][C:17]1[CH:18]=[C:19]2[C:23](=[CH:24][CH:25]=1)[NH:22][CH:21]=[C:20]2[CH2:26][CH2:27][NH:28][C:12]([C:9]1[CH:8]=[C:7]([CH2:6][Cl:15])[O:11][N:10]=1)=[O:14]

Participants

Conditions

Temperature: 80 °C

Procedure

Thionyl chloride (0.5 mL; 7.26 mmol) was added to a mixture of 5-(hydroxymethyl)isoxazole-3-carboxylic acid (0.207 g; 7.26 mmol) and stirred at 80° C. for 72 h. The solution was concentrated under reduced pressure and the crude material was dissolved in dichloromethane (5 mL) and added to a mixture of 2-(5-chloro-1H-indol-3-yl)ethanamine hydrochloride (0.370 g; 1.60 mmol) and triethylamine (0.524 mL; 3.62 mmol) in dichloromethane (5 mL). The resulting solution was stirred at room temperature for 20 min, concentrated under reduced pressure and the crude material was purified by flash chromatography on silica gel (eluent 2 to 20% ethyl acetate in dichloromethane) to afford N-(2-(5-chloro-1H-indol-3-yl)ethyl)-5-(chloromethyl)isoxazole-3-carboxamide 0.088 g (22%).

Workup

concentrationThe solution was concentrated under reduced pressure
dissolutionthe crude material was dissolved in dichloromethane (5 mL)
stirringThe resulting solution was stirred at room temperature for 20 min
concentrationconcentrated under reduced pressure
customthe crude material was purified by flash chromatography on silica gel (eluent 2 to 20% ethyl acetate in dichloromethane)

Sources & evidence

ORD record: ord-3f31bf62192c46e889b5c6eb27cf5023
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08618138B2

Linked notes

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